Crystal structure of plant vacuolar iron transporter VIT1
Crystal structure of plant vacuolar iron transporter VIT1
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DOI：
10.1038/s41477-019-0367-2
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发表时间：
2019-03-01
期刊：
影响因子：
18
通讯作者：
Nureki, Osamu
中科院分区：
文献类型：
--
作者：
Kato, Takafumi;Kumazaki, Kaoru;Nureki, Osamu
铁离子在一些重要的酶促反应中是必不可少的辅助因子，如DNA复制、氧运输、呼吸和光合电子转移链，但其过量积累会引起细胞氧化应激。液泡铁转运蛋白1 （Vacuolar iron transporter 1, VIT1）通过将细胞质中的铁离子转运到液泡中，对植物体内铁的稳态起着重要作用。通过对VIT1基因的修饰，提高了作物的铁含量，可用于治疗人类缺铁疾病。此外，来自疟原虫的VIT1被认为是治疗疟疾的潜在药物靶点。本文报道了大桉树玫瑰胶中VIT1的晶体结构，它可能是一个依赖H+的Fe2+和其他过渡金属离子的反转运体。VIT1采用了一种新的蛋白质折叠，形成了一个由五个跨膜结构域组成的二聚体，由二聚体界面上保守的蛋氨酸和羧酸残基构成离子转运途径。第二个跨膜螺旋从脂质膜突出约40埃，并连接到一个三螺旋束，三角形细胞质结构域，它与底物金属离子结合并稳定其可溶性形式，因此在它们的运输中起重要作用。这些机制的见解将为进一步设计转基因作物和开发抗疟疾药物提供有用的信息。
The iron ion is an essential cofactor in several vital enzymatic reactions, such as DNA replication, oxygen transport, and respiratory and photosynthetic electron transfer chains, but its excess accumulation induces oxidative stress in cells. Vacuolar iron transporter 1 (VIT1) is important for iron homeostasis in plants, by transporting cytoplasmic ferrous ions into vacuoles. Modification of the VIT1 gene leads to increased iron content in crops, which could be used for the treatment of human iron deficiency diseases. Furthermore, a VIT1 from the malaria-causing parasite Plasmodium is considered as a potential drug target for malaria. Here we report the crystal structure of VIT1 from rose gum Eucalyptus grandis, which probably functions as a H+-dependent antiporter for Fe2+ and other transition metal ions. VIT1 adopts a novel protein fold forming a dimer of five membrane-spanning domains, with an ion-translocating pathway constituted by the conserved methionine and carboxylate residues at the dimer interface. The second transmembrane helix protrudes from the lipid membrane by about 40 angstrom and connects to a three-helical bundle, triangular cytoplasmic domain, which binds to the substrate metal ions and stabilizes their soluble form, thus playing an essential role in their transport. These mechanistic insights will provide useful information for the further design of genetically modified crops and the development of anti-malaria drugs.